Phenyl isothiocyanate derivatives and their production

ABSTRACT

A compound of the formula: ##STR1## wherein X is oxygen or sulfur; 
     R 1  is hydroxy, C 1  -C 4  alkoxy, phenoxy, amino, C 1  -C 4  alkylamino, C 2  -C 8  dialkylamino, C 6  -C 10  arylamino, tetrahydrofurfurylamino, morpholino or methylpiperazino, but when X is sulfur R 1  must be amino, C 1  -C 4  alkylamino, C 2  -C 8  dialkylamino or morpholino; 
     R 2  is C 1  -C 4  alkoxy or C 2  -C 5  alkoxycarbonyl; 
     R 3  is hydrogen C 1  -C 4  alkyl, C 1  -C 4  alkoxy, C 2  -C 8  dialkylamino or halogen 
     and its salts being useful as agricultural fungicides are provided.

The present invention relates to phenyl isothiocyanate derivatives. Somephenyl isothiocyanates have heretofore been known in Belgian Pat. No.741,448; Canadian Patent 807,601; French Pat. No. 1,545,679; GermanPatent 2,013,788; British Pat. No. 1,183,113; Japanese PatentPublication No. 4,523/1973; Japanese Patent Unexamined Publications Nos.18,626/1975; 1,023/1977; Dutch Pat. No. 67.12996; U.S. Pat. Nos.3,530,161; 3,887,358, etc.

More particularly, this invention is directed to a compound of theformula: ##STR2## wherein X is oxygen or sulfur;

R¹ is hydroxy C₁ -C₄ alkoxy, phenoxy, amino, C₁ -C₄ alkylamino, C₂ -C₈dialkylamino, C₆ -C₁₀ arylamino, tetrahydrofurylamino, morpholino ormethylpiperazino, but when X is sulfur R¹ must be amino, C₁ -C₄alkylamino, C₂ -C₈ dialkylamino or morpholino;

R² is C₁ -C₄ alkoxy or C₂ -C₅ alkoxycarbonyl;

R³ is hydrogen, C₁ -C₄ alkyl, C₁ -C₄ alkoxy, C₂ -C₈ dialkylamino orhalogen; and their salts being useful as agricultural fungicides.

Giving some additional explanations to the terms in the foregoingdefinition, "alkyl" refers to methyl, ethyl, propyl, isopropyl, butyl,isobutyl, t-butyl and the like; "alkoxy" refers to methoxy, ethoxy,propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy and the like;"alkylamino" refers to methylamino, ethylamino, propylamino,isopropylamino, butylamino and the like; "dialkylamino" refers todimethylamino, methylethylamino, diethylamino, ethylbutylamino,dibutylamino and the like; "arylamino" refers to phenylamino,tolylamino, xylylamino, mesitylamino, cumenylamino and the like;"alkoxycarbonyl" refers to methoxycarbonyl, ethoxycarbonyl,propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl and the like;"halogen" refers to fluoro, chloro, bromo, iodo and the like.

Up to this time, it has been known that such phenyl isothiocyanates areuseful as germination regulators (Japanese Patent Unexamined PublicationNo. 1023/1977), and that p-ethoxycarbonylphenyl isothiocyanates areuseful as agricultural fungicides (Canadian Pat. No. 807,601). However,the fungicidal activity of these compounds is insufficient foragricultural use.

The phenyl isothiocyanate derivatives (I) of the present invention aresynthesized as shown in the following reaction scheme: ##STR3## whereinR¹, R² and R³ are each as defined above. Route I

The isothiocyanate formation may be carried out in a conventionalmanner. The starting material (II) is reacted with carbon disulfide anda base (e.g. triethylamine, pyridine, dimethylamine) in an organicsolvent, and the resulting intermediate is reacted with an alkylhalogenocarbonate (e.g. ethyl chlorocarbonate, methyl chlorocarbonate)with or without organic solvent. Thus phenyl isothiocyanates (Ia) areobtained.

Alternatively the phenyl isothiocyanates (Ia) are prepared by reactingthe starting material (II) with a dialkylthiocarbamoyl halogenide (e.g.diethylthiocarbamoyl chloride) in an organic solvent.

The starting material (II) can be prepared by known methods. Forexample, 3-diethylcarbamoyl-4-methoxy-5-methylaniline is prepared from2-methoxy-3-methyl-5-nitrobenzoyl chloride by two steps as follows:##STR4## Route II

The convertion of carbamoyl group into thiocarbamoyl group is carriedout by treating the starting material (II) with phosphorus pentasulfidein an organic solvent. Thus, thiocarbamoyl compound (III) is obtained.

Route III

The above obtained thiocarbamoyl compound (III) is subjected to theisothiocyanate formation. This route may be carried out in accordancewith the procedure given in Route I. The thiocarbamoylaniline (III) canbe obtained by reducing the corresponding nitrobenzene derivative:##STR5## wherein R¹, R² and R³ are each as defined above. Thus, anotherproduct (Ib) is obtained.

Route IV

The first product (Ia) is subjected to the thiocarbamoyl groupformation. This route may be carried out by treating with phosphoruspentasulfide or with a dialkylthiocarbamoyl halogenide/aluminum chlorideeach in an organic solvent. Thus, the second product (Ib) is obtained,too.

Route V

The second product (Ib) is directly prepared by treating the startingmaterial (II) with a dialkylthiocarbamoyl halogenide/aluminum chloridein an organic solvent.

Any of these reactions are carried out at a temperature of about 0°-150°C., preferably 45°-100° C. Representatives of the organic solventinclude tetrahydrofuran, benzene, toluene, ethylene dichloride,methylene chloride, chlorobenzene and the like.

Presently preferred and practical embodiments of the present inventionare illustratively shown in the following examples.

EXAMPLE 1

To a solution of methyl 2-methoxy-4-methyl-5-aminobenzoate (975 mg) intetrahydrofuran (5 ml) are added triethylamine (1.52 g) and carbondisulfide (1.14 g), and the resultant mixture is stirred at roomtemperature for 2.5 hours. Ethyl chlorocarbonate (1.63 g) is added tothe mixture, which is stirred for additional 20 minutes at roomtemperature. A solution of sodium hydroxide (1.2 g) in water (32 ml) isadded to the mixture, which is stirred for 15 minutes. The reactionmixture is mixed with an excess amount of water and shaken withmethylene chloride. The organic layer is dried over Glauber's salt andthe solvent is evaporated. The residue is dissolved in methylenechloride and chromatographed on a column of silica gel. Evaporating thesolvent from the elution, the residue is dissolved in isopropyl etherand n-hexane is added thereto. The precipitated crystals are filtered togive 3-methoxycarbonyl-4-methoxy-6-methylphenyl isothiocyanate (952 mg)as crystals melting at 86°-87.5° C.

EXAMPLES 2-27

Using the following starting material (II), the reaction is carried outas in Example 1, whereby the corresponding product (Ia) is obtained:

    ______________________________________                                         ##STR6##                                                                                                   Ia                                              Ex.  II                      mp(°C.) or                                No.  R.sup.1     R.sup.2  R.sup.3a                                                                           R.sup.3b                                                                            IR(cm.sup.-1)                            ______________________________________                                        2    OMe         OMe      H    H     78.5-79.5                                3    OMe         OMe      H    OMe   92-93                                    4    OMe         OMe      Me   H     2100, 1728                                                                    (CHCl.sub.3)                             5    OMe         OMe      OMe  H     64-65                                    6    OEt         OMe      H    Me    60.5-61.5                                7    OMe         OEt      H    Me    91-92                                    8    O-i-Pr      OMe      H    Me    2080, 1722                                                                    (film)                                   9    DMA         OMe      H    H     2100, 1630                                                                    (CHCl.sub.3)                             10   DMA         OMe      H    Me    161-162                                  11   DMA         OMe      H    OMe   184-185.5                                12   DMA         OMe      Me   H     74.0-75.0                                13   DMA         OMe      OMe  H     2100, 1629                                                                    (CHCl.sub.3)                             14   OPh         OMe      H    Me    174.5-175.5                              15                                                                                  ##STR7##   OMe      H    Me    162.5-163.5                              16                                                                                  ##STR8##   OMe      H    Me    155.5-156.5                              17   NHMe        OMe      H    Me    191.5-192.5                              18   NHMe        OMe      H    OMe   187-188                                  19   NHMe        OMe      Me   H     128-129                                  20   NHMe        OMe      OMe  H     129-130                                  21   NH.sub.2    OMe      H    Me    206-207                                  22   NH.sub.2    OMe      H    OMe   224-226                                  23   NH.sub.2    OMe      OMe  H     161-162                                  24   OMe         COOEt    H    H     1728, 1760,                                                                   2090 (film)                              25   DEA         OMe      H    H     90-91                                    26   DEAEA       OMe      H    Me    93-94                                    27   OMe         OMe      H    DMA   103-103.5                                ______________________________________                                         Note:                                                                         The abbreviations in the Table have the following meanings: H (hydrogen),     Me (mrthyl group), Et (ethyl group), Pr (propyl group), Ph (phenyl group)     DMA (dimethylamino group), DEA (diethylamino group), DEAEA                    (diethylaminoethylamino group), i (iso), mp (melting point), IR (infrared     spectrum).                                                               

EXAMPLE 28

A mixture of3-[N-(2,6-dimethylphenyl)carbamoyl]-4-methoxy-6-chloroaniline (650 mg),diethylthiocarbamoyl chloride (360 mg) and chlorobenzene (6 ml) isrefluxed for 30 minutes. The reaction mixture is mixed with water andshaken with methylene chloride. The organic layer is washed with water,dried over Glauber's salt and concentrated to remove the solvent. Theresidue is chromatographed on a column of silica gel, which is elutedwith methylene chloride. The eluted fractions are collected and thesolvent is evaporated. The residue is recrystallized from ethyl acetateto give 3-[N-(2,6-dimethylphenyl)carbamoyl]-4-methoxy-6-chlorophenylisothiocyanate (340 mg) as crystals melting at 191°-192.5° C.

EXAMPLE 29-33

Using the following starting material (II), the reaction is carried outas in Example 28, whereby the following product (Ia) is obtained:

    ______________________________________                                         ##STR9##                                                                     Ex.   II                      Ia                                              No.   R.sup.1         R.sup.2 R.sup.3b                                                                            mp(°C.)                            ______________________________________                                        29    OMe             OMe     Cl    98-99                                     30    DMA             OMe     Cl      195-196.5                               31    NHMe            OMe     Cl    192-195                                   32                                                                                   ##STR10##      OMe     Cl    167-168                                   33    OH              OMe     Me    181-183                                   ______________________________________                                         Note:                                                                         The abbreviations in the Table have the same meanings as defined above.  

EXAMPLE 34

(a) To a solution of 3-dimethylcarbamoyl-4-methoxy-5-methylnitrobenzene(1.10 g) in benzene (11 ml) is added phosphorus pentasulfide (3.08 g),and the resultant mixture is refluxed for 1 hour. After sooling, thereaction mixture is mixed with icy water and shaken with ether. Theorganic layer is washed with water, dried over Glauber's salt andconcentrated under reduced pressure to remove the solvent. The residueis chromatographed on a column of silica gel, which is eluted withbenzene, methylene chloride and then methylene chloride/2% methanol inorder. The eluted fractions are concentrated under reduced pressure andthe residue is washed with isopropyl ether to give3-dimethylthiocarbamoyl-4-methoxy-5-methyl-nitrobenzene (1.0 g) ascrystals melting at 138°-139° C.

(b) To a solution of above product (0.95 g) in methanol (30 ml) is addedplatinum dioxide hydrate (0.20 g), and the resultant mixture is shakenin hydrogen stream, until the absorption of hydrogen stops. The reactionmixture is filtered to remove the catalyst and the filtrate isconcentrated under reduced pressure. The residue is dissolved inmethylene chloride, dried over Glauber's salt and the solvent isevaporated. The residue is dissolved in dry tetrahydrofuran (5 ml) togive a solution, which is mixed with triethylamine (1.13 g) and carbondisulfide (0.85 g). The resultant mixture is stirred at ordinarytemperature overnight. Ethyl chlorocarbonate (1.22 g) is added to themixture under cooling, which is stirred for 45 minutes under cooling.The mixture is treated with 10% aqueous sodium hydroxide (9 ml) andshaken with methylene chloride. The organic layer is washed with water,dried over Glauber's salt and the solvent is evaporated. The residue ischromatographed on a column of silica gel, which is eluted withmethylene chloride. After evaporating the solvent, the fraction affordsa brown oil (0.87 g), which is recrystallized from isopropyletherpetroleum ether to give3-dimethylthiocarbamoyl-4-methoxy-5-methylphenyl isothiocyanate (312 mg)as crystals melting at 74°-75° C.

EXAMPLE 35

To a solution of 3-dimethylcarbamoyl-4-methoxy-5-methylaniline (600 mg)in dry ethylene dichloride (12 ml) is added diethylthiocarbamoylchloride (850 mg), and the resultant mixture is refluxed for 25 minutes.Aluminum chloride (360 mg) is added to the mixture, which is refluxedfor 2 hours. After cooling, the mixture is mixed with aqueous sodiumbicarbonate, stirred at room temperature for 15 minutes and shaken withmethylene chloride. The organic layer is washed with water, dried overGlauber's salt and the solvent is evaporated under reduced pressure. Theresidue is chromatographed on a column of silica gel, which is elutedwith methylene chloride. The eluted fraction is evaporated, and theresidue is washed with isopropyl ether-petroleum ether to give3-dimethylthiocarbamoyl-4-methoxy-5-methylphenyl isothiocyanate (214 mg)as crystals melting at 74°-75° C.

EXAMPLE 36

Using 3-diethylcarbamoyl-4-methoxyphenyl isothiocyanate (700 mg), thereaction is carried out as in Example 35, whereby3-diethylthiocarbamoyl-4-methoxyphenyl isothiocyanate (437 mg) isobtained as colorless needles melting at 121°-122° C.

EXAMPLES 37-39

The following compounds are obtained by carrying out the reaction as inExample 34 (a).

    ______________________________________                                        Ex.                                                                           No.                                                                           ______________________________________                                        37                                                                                   ##STR11##           m.p. 202.5-204° C.                          38                                                                                   ##STR12##           m.p. 165-166° C.                            39                                                                                   ##STR13##           m.p. > 250° C.                              ______________________________________                                    

The phenyl isothiocyanates (I) are useful as agricultural fungicidesagainst various phytopathogenic fungi such as cucurbitaceae powderymildew, cucurbitaceae downy mildew, cucurbitaceae anthracnose, riceplant blast and drooping diseases of various crops. Excellent controleffect of the product (I) is illustratively shown by the followingexperiments. The list indicates test compounds used in the experiments.

    __________________________________________________________________________    Compd.                                                                        No.  Structural Formula                                                                            Chemical Name                                                                             Note                                         __________________________________________________________________________          ##STR14##      3-Methoxycarbonyl- 4-methoxyphenyl isothiocyanate              ##STR15##      3-Methoxycarbonyl- 4-methoxy-6-methyl- phenyl                                 isothiocyanate                                                 ##STR16##      3-Methoxycarbonyl- 4,6-dimethoxyphenyl isothiocyanate                         1                                                              ##STR17##      3-Methoxycarbonyl- 4,5-dimethoxyphenyl isothiocyanate                         2                                                              ##STR18##      3-Dimethylcarbamoyl- 4-methoxyphenyl isothiocyanate            ##STR19##      3-Isopropoxycarbonyl- 4-methoxy-6-methyl- phenyl                              isothiocyanate                                                 ##STR20##      3-Methoxycarbonyl- 4-methoxy-5-methyl- phenyl                                 isothiocyanate                                                 ##STR21##      3-Methoxycarbonyl- 4-ethoxy-6-methyl- phenyl                                  isothiocyanate                                                 ##STR22##      3-Ethoxycarbonyl- 4-methoxy-6-methyl- phenyl                                  isothiocyanate                                           10.                                                                                 ##STR23##      Manganese ethylene bisdithiocarbamic acid                                                 control)                                           ##STR24##      N'-Dichlorofluoro- methylthio-N,N-di- methyl-N'-pheny                         l- sulfamide (dichlo- fluanide)                                                           control                                            ##STR25##      6-Methyl-1,3-dithiolo- [4,5-b]-quinoxalin-2- on                               (quinomethionate)                                                                         control                                            ##STR26##      p-Ethyl-s,s-diphenyl- phosphorodithiolate (EDDP)                                          control                                            ##STR27##      3-Hydroxy-5-methyl-  isoxazole (hydroxyisoxazole)                                         control                                      __________________________________________________________________________

EXPERIMENT 1 Test for control effect against cucumber anthracnose

Seeds of cucumber (cultivar: Matsukaze) were sown in a vinylchloride-cup of 9 cm in diameter containing soil, one seed per cup, in agreenhouse. When the primary leaf was developed, 5 ml of a solution ofthe test compound at a prescribed concentration was applied per cup.After application, the cups were kept at a temperature of 25°-26° C. andhumidity of 80% for 1 day. A spore suspension of cucumber anthracnose(Colletotrichum lagenarium) was inoculated onto the aforementionedprimary leaves of cucumber, five spots per leaf. The cups were kept at atemperature of 25° C. and humidity of 95% for 1 day. After allowing tostand at a temperature of 25° C. and humidity of 75-80% for 6 days,diseased degree in the inoculated portions was observed. Percent diseasecontrol was calculated using the following formula: ##EQU1##

Results are indicated in Table 1.

                  TABLE 1                                                         ______________________________________                                                                           Percent                                                                       Disease                                    Test Compound                                                                           Concentration            Control                                    No.       (ppm)       Diseased Degree                                                                            (%)                                        ______________________________________                                        1         500         0            100.0                                      2         500         0            100.0                                      3         500         0            100.0                                      4         500         0            100.0                                      8         500         0            100.0                                      9         500         0            100.0                                      10        1440        0            100.0                                      Untreated Plot                                                                          --          25            0.0                                       ______________________________________                                    

EXPERIMENT 2 Test for control effect against cucumber downy mildew

Seeds of cucumber (cultivar: Matsukaze) were sown in a vinylchloride-cup of 9 cm in diameter containing soil, one seed per cup, in agreenhouse. When the primary leaf was developed, 5 ml of the solution ofthe test compounds at a prescribed concentration was applied per cup.After application, the cups were kept at a temperature of 20°-22° C. for1 day. A spore suspension of cucumber downy mildew (Pseudoperonosporacubensis) was inoculated onto the aforementioned primary leaves ofcucumber, five spots per leaf. The cups were kept at a temperature of20° C. and humidity of 95% for 10 days. Diseased degree in theinoculated portions was observed. Percent disease control was calculatedusing the following formula: ##EQU2##

Results are indicated in Table 2.

                  TABLE 2                                                         ______________________________________                                                                           Percent                                                                       Disease                                    Test Compound                                                                           Concentration            Control                                    No.       (ppm)       Diseased Degree                                                                            (%)                                        ______________________________________                                        1         500         0            100                                        2         500         0            100                                        3         500         0            100                                        4         500         0            100                                        6         500         0            100                                        8         500         0            100                                        11        500         0            100                                        Untreated Plot                                                                          --          100          0                                          ______________________________________                                    

EXPERIMENT 3 Test for control effect against cucumber powdery mildew

Seeds of cucumber (cultivar: Matsukaze) were sown in a vinylchloride-cup of 9 cm in diameter containing soil, one seed per cup, in agreenhouse. When the primary leaf was developed, 5 ml of the solution ofthe test compounds at a prescribed concentration was applied per cup.After application, the cups were kept at a temperature of 25°-26° C. for1 day. Leaves of cucumber infected by pathogenic fungi of the powderymildew (Sphaerotheca fuliginea) were taken, and lesions covered withoidia were cut out in 1 square centimeter pieces. The fungi wereinoculated to the primary leaves in the cups by sticking the oidiacovered pieces onto them, four plots per leaf. The cups were then keptat a temperature of 25°-26° C. for 10 days. The oidium formation on theinoculated leaves was observed by microscope.

+: Infected spots and formation of numbers of oidia observed on theinoculated portions.

-: Neither infected spot nor oidium formation observed

Results are indicated in Table 3.

                  TABLE 3                                                         ______________________________________                                        Test Compound                                                                             Concentration                                                     No.         (ppm)         Diseased Degree                                     ______________________________________                                        1           500           -                                                   2           500           -                                                   3           500           -                                                   4           500           -                                                   7           500           -                                                   8           500           -                                                   12          125           -                                                   Untreaed Plot                                                                             --            +                                                   ______________________________________                                    

EXPERIMENT 4 Test for control effect against rice plant blast

Seedlings of rice plant (cultivar: Aichi-asahi), reared for 10 days inthe greenhouse, were transplanted in a vinyl chloride-cup of 12 cm indiameter containing soil. A solution of the test compound at aprescribed concentration was applied 14 days after the transplantation.One day after the application, a spore suspension of pathogenic fungi ofrice plant blast (Pyricularia oryzae) was sprayed on the leaf blade ofthe seedilings. The cups were kept in an infection room at a temperatureof 28° C. and humidity of 98% for 24 hours. Then, they were kept at atemperature of 28° C. and humidity of 90% for 7 days in a greenhouse.Number of spots on the inoculated leaves was observed, and percentdisease control was calculated using the following formula: ##EQU3##

Results are indicated in Table 4.

                  TABLE 4                                                         ______________________________________                                                                           Percent                                                                       Disease                                    Test Compound                                                                            Concentration                                                                              Number of  Control                                    No.        (ppm)        Spots      (%)                                        ______________________________________                                        1          500          4          99.8                                       2          500          92         96.3                                       3          500          11         99.6                                       4          500          4          99.8                                       5          500          23         99.1                                       6          500          143        94.3                                       8          500          331        86.8                                       9          500          567        77.4                                       13         300          17         99.3                                       Untreated Plot                                                                           --           2515       0                                          ______________________________________                                    

EXPERIMENT 5 Test for control effect against damping-off of cucumberseedlings

One hundred and fifty ml of sterile soil was placed into a pot of 9 cmin diameter, and 20 cucumber seeds were sowed per pot. After cultivatingfungi of the cucumber damping-off (Pythium aphanidermatum, Fusariumoxysoirum, Rhizoctonia solani) in a wheat bran medium for 5 days, it wasmixed with sterile soil and cultured again for 2 days at a temperatureof 25° C. Thirty ml of the solution of the test compounds at aprescribed concentration was drenched to each pot. The pots were kept ata temperature of 28° C. for 11 days in a greenhouse. Diseased degree inthe treated pots was observed. Diseased degree and percent diseasecontrol were calculated using the following formulae:

Index of damping-off

1 Not germinated

2 Wilt and rot

3 Invasion more than 1/3 seedlings

4 Invasion not more than 1/3 seedlings

5 Seedlings sound ##EQU4##

Results are indicated in Table 5.

                                      TABLE 5                                     __________________________________________________________________________             Rhizoctonia solani                                                                      Pythium aphanidermatum                                                                    Fusarium oxysporum                             Test          Percent    Percent    Percent                                   Com-                                                                              Concen-   Disease    Disease    Disease                                   pound                                                                             tration                                                                            Diseased                                                                           Control                                                                            Diseased                                                                            Control                                                                             Diseased                                                                           Control                                   No. (ppm)                                                                              Degree                                                                             (%)  Degree                                                                              (%)   Degree                                                                             (%)                                       __________________________________________________________________________    1   500  28.8 71.2 36.3  63.7  65.0 7.9                                       4   500  0    100  76.3  23.7  10.0 85.8                                      5   500  36.3 63.7 0     100   22.5 68.1                                      6   500  28.8 71.2 85.0  15.0  10.0 85.8                                      7   500  56.3 43.7 100   0     27.5 61.0                                      8   500  66.0 34.0 100   0     18.8 73.4                                      14  500  62.5 37.5 21.3  78.7  25.0 64.6                                      Un-                                                                           treat-                                                                        ed                                                                            Plot                                                                              --   100  0    100   0     100  0                                         __________________________________________________________________________

Accordingly, the phenyl isothiocyanates (I) showed patent fungicidalactivity against cucumber anthracnose, cucmber downy mildew, cucumberpowdery mildew, rice plant blast, and damping-off of cucumber seedlings.The other compounds (I) also showed similar fungicidal activity.

The product (I) of this invention may be applied in a form suitable foragricultural fungicides, such as emulsions, solutions, wettable powders,dusts, suspensions, granules, aerosols, oils, smokes, pastes and thelike. The compound (I) may be applied singly or in combination withsolid or liquid carriers. Representatives of the solid carriers includeclay, talc, diatomaceous earth, silica, kaolin, bentonite, pumice andthe like. Examples of the liquid carriers are water, methanol, ethanol,ethylene glycol, dimethylformamide, dimethylsulfoxide, acetone, methylethyl ketone, cellosolve, dioxane, diglyme, and the like. If necessary,there may be added appropriate adjuvants such as emulsifiers,dispersants, spreaders, surfactants, wetting agents, stabilizers,synergists and the like. Moreover, the compound (I) may be used incombination with other agricultural chemicals such as other fungicides,germicides, insecticides, herbicides, repellents, miticides,nematocides, plant growth regulators and the like. Application rate ofthe compound (I) for liquid formulations is in the range of about50-2,000 ppm, preferably 100-1,000 ppm and about 100-200 L per 10 are;and application rate for solid formulations is about 3-4 kg per 10 are.

Fungicidal compositions containing the compound (I) are illustrativelyshown in the following Formulations.

Formulation 1

Fifty parts by weight of 3-methoxycarbonyl-4-methoxyphenylisothiocyanate, 35 parts by weight of diatomaceous earth, 10 parts byweight of white carbon, 2 parts by weight of sodiumalkylbenzenesulfonate and 3 parts by weight of calcium lignin sulfonateare triturated and mixed to provide wettable powder.

Formulation 2

Thirty parts by weight of 3-methoxycarbonyl-4,6-dimethoxyphenylisothiocyanate, 40 parts by weight of xylene, 20 parts by weight ofcyclohexanone, and 10 parts by weight of polyoxyethylene alkyl arylether are mixed and stirred to provide an emulsion.

Formulation 3

Three parts by weight of 3-methoxycarbonyl-4,5-dimethoxyphenylisothiocyanate, 7 parts by weight of talc and 90 parts by weight of clayare mixed and triturated to provide a dust formulation.

Formulation 4

Three parts by weight of 3-methoxycarbonyl-4,6-dimethoxyphenylisothiocyanate, 2 parts by weight of sodium alkylbenzenesulfonate, 45parts by weight of clay and 50 parts by weight of bentonite are mixed,kneaded with a suitable amount of water and granulated by an extrusivegranulator. Air-drying at 50° C. and sieving through a 20-40 mesh screenprovides the desired granules. Such granules are directly applied.

Further, the phenyl isothiocyanates (I) are also hopeful as antifungalagents in humans and animals. For example,3-methoxycarbonyl-4,5-dimethoxyphenyl isothiocyanate showed a minimuminhibitory concentration of 6.2 γ/ml against Candida albicans M-9 in invitro test.

What is claimed is:
 1. A compound of the formula: ##STR28## wherein X isoxygen or sulfur;R¹ is phenoxy, amino, methylamino, ethylamino,propylamino, isopropylamino, butylamino, dimethylamino,methylethylamino, diethylamino, ethylbutylamino, dibutylamino,phenylamino, tolylamino, xylylamino, mesitylamino, cumenylamino,tetrahydrofurfurylamino, morpholino or methylpiperazino, but when X issulfur R¹ is amino, methylamino, ethylamino, propylamino,isopropylamino, butylamino, dimethylamino, methylethylamino,diethylamino, ethylbutylamino, dibutylamino, or morpholino; R² ismethoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy or t-butoxy; R³is hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl,methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, t-butoxy,dimethylamino, methylethylamino, diethylamino, ethylbutylamino,dibutylamino, fluoro, chloro, bromo or iodo;and salts thereof.
 2. Acompound according to claim 1, namely3-dimethylcarbamoyl-4-methoxyphenyl isothiocyanate.
 3. A compoundaccording to claim 1, namely 5-dimethylcarbamoyl-4-methoxy-2-tolylisothiocyanate.
 4. A compound according to claim 1, namely2,4-dimethoxy-5-dimethylcarbamoylphenyl isothiocyanate.
 5. A compoundaccording to claim 1, namely 5-dimethylcarbamoyl-4-methoxy-3-tolylisothiocyanate.
 6. A compound according to claim 1, namely,3,4-dimethoxy-5-dimethylcarbamoylphenyl isothiocyanate.
 7. A compoundaccording to claim 1, namely 4-methoxy-5-phenoxycarboxyl-2-tolylisothiocyanate.
 8. A compound according to claim 1, namely4-methoxy-5-morpholinocarbonyl-2-tolyl isothiocyanate.
 9. A compoundaccording to claim 1, namely4-methoxy-5-(4-methylpiperazinocarbonyl)-2-tolyl isothiocyanate.
 10. Acompound according to claim 1, namely4-methoxy-5-methylcarbamoyl-2-tolyl isothiocyanate.
 11. A compoundaccording to claim 1, namely 2,4-dimethoxy-5-methylcarbamoylphenylisothiocyanate.
 12. A compound selected from the group consisting of(a)4-methoxy-5-methylcarbamoyl-2-tolyl isothiocyanate; (b)3,4-dimethoxy-5-methylcarbamoylphenyl isothiocyanate; (c)5-carbamoyl-4-methoxy-2-tolyl isothiocyanate; (d)5-carbamoyl-2,4-dimethoxyphenyl isothiocyanate; (e)5-carbamoyl-3,4-dimethoxyphenyl isothiocyanate; (f)3-dimethylcarbamoyl-4-methoxyphenyl isothiocyanate; (g)3-[N-(2,6-dimethylphenyl)carbamoyl]-4-methoxy-6-chlorophenylisothiocyanate; (h) 2-chloro-5-dimethylcarbamoyl-4-methoxyphenylisothiocyanate; (i) 2-chloro-5-methylcarbamoyl-4-methoxyphenylisothiocyanate; and (j)2-chloro-4-methoxy-5-(2,3,4,5-tetrahydrofurfuryl)carbamoylphenylisothiocyanate.
 13. A compound selected from the group consisting of(a)3-dimethylthiocarbamoyl-4-methoxy-5-methylphenyl isothiocyanate and (b)3-diethylthiocarbamoyl-4-methoxyphenyl isothiocyanate.
 14. A compoundaccording to claim 1, namely3-dimethylcarbamoyl-4-methoxy-5-methylphenyl isothiocyanate.
 15. Acompound according to claim 1, wherein X is sulfur; R¹ is amino,methylamino, dimethylamino or morpholino; R² is methoxy; and R³ ishydrogen, chlorine, methyl or methoxy.
 16. A compound according to claim15, namely 3-thiocarbamoyl-4,6-dimethoxyphenyl isothiocyanate.
 17. Acompound according to claim 15, namely3-methylthiocarbamoyl-4,6-dimethoxyphenyl isothiocyanate.
 18. A compoundaccording to claim 15, namely3-morpholinothiocarbonyl-4-methoxy-5-methylphenyl isothiocyanate.